Method of collecting and preserving a biological sample

ABSTRACT

A biological sample collection system can include (i) a sample collection vessel having an opening for receiving a biological sample, (ii) a selectively movable valve comprising a core and a collar disposed about the core, and (iii) a sealing cap coupled to the collar and comprising a reagent chamber for storing a measure of sample preservation reagent. The sealing cap is configured to associate—and form a fluid tight connection—with the sample collection vessel such that associating the sealing cap with the sample collection vessel causes a physical rearrangement of the core relative to the collar such that a fluid vent associated with the core is moved into fluid communication with the reagent chamber, thereby permitting sample preservation reagent to pass from the regent chamber to the sample collection vessel.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a division of U.S. patent application Ser. No.17/093,815, filed Nov. 10, 2020, which is a continuation of U.S. patentapplication Ser. No. 16/906,830, filed Jun. 19, 2020, which claims thebenefit of U.S. Provisional Application No. 62/864,500, filed Jun. 20,2019, which are incorporated by reference in their entirety.

BACKGROUND Technical Field

This disclosure generally relates to vials and vessels for collectingand storing biological samples. More specifically, the presentdisclosure relates to systems and kits for the collection andpreservation of biological samples for future testing in a laboratory orother biological sample analysis facility.

Background and Relevant Art

Field collection of biological samples can provide scientists,physicians, geneticist, epidemiologists, or similar personnel withinvaluable information. For example, access to a fresh sample of apatient's blood, purulent discharge, or sputum can help a physician orepidemiologist to isolate or identify a causative agent of infection.Similarly, a saliva sample can permit a scientist or geneticist accessto the requisite nucleic acid for genetic sequencing, phylotyping, orother genetic-based studies. In the foregoing examples, in addition tomany other situations, it is desirable to work with a fresh biologicalsample to ensure procurement of accurate results. However, isolation ofthe probative composition (e.g., nucleic acid, proteins, chemicals,etc.) often requires use of specialized equipment and often benefitsfrom controlled laboratory conditions.

It can be inconvenient and sometimes improbable to requirepatients/individuals to travel to a biological sample collection centerhaving the appropriate equipment and desirable controlled environmentfor sample preparation. Similarly, it may be difficult for personnel todirectly access the patient/individual, particularly if the sample sizeis large and/or geographically diverse (e.g., as can be found in largegenetic studies of thousands of individuals across an entire country,ethnic population, or geographic region). Further complicating thisissue, it is often beneficial to immediately process any procuredbiological sample, and field personnel may be limited by lack of accessto appropriate specialized equipment or to a controlled environment forhigh-fidelity sample processing.

Some biological sample collection devices and kits have addressed someof the foregoing issues. For example, some commercial kits provide auser with a vial for receiving a biological sample and a preservationreagent that can be added to the collected biological sample, acting topreserve elements within the biological sample (to a certain extent andfor a period of time). However, implementations of self-collectionsystems often rely on inexperienced or untrained individuals to depositthe biological sample into the receiving vessel. This presents a numberof problems, including, for example, technical training and precisemeasurements often required to properly preserve the biological samplefor later processing. In the absence of such, it is important to providea biological sample collection system that can be easily implemented bya novice user and which can preserve the received biological sample forlater processing.

Accordingly, there are a number of disadvantages with biological samplecollection and preservations systems that can be addressed.

BRIEF SUMMARY

Implementations of the present disclosure solve one or more of theforegoing or other problems in the art with kits, apparatuses, andmethods for collecting and preserving a biological sample. Inparticular, one or more implementations can include a biological samplecollection system—or a kit including the same—for collecting andpreserving a biological sample.

In some embodiments, a biological sample collection system can include asample collection vessel having an opening for receiving a biologicalsample, a selectively movable valve comprising a core and a collardisposed about the core that is configured to at least partiallyassociate with the opening of the sample collection vessel, and asealing cap configured to associate with the selectively movable valveand with the sample collection vessel. The sealing cap can include areagent chamber for storing a measure of sample preservation reagent.Associating the sealing cap with the sample collection vessel causes aphysical rearrangement of the core relative to the collar such that afluid vent associated with the core is moved into fluid communicationwith the reagent chamber, thereby permitting sample preservation reagentto pass from the regent chamber to the sample collection vessel.

In other embodiments, a biological sample collection system can includea sample collection vessel having an opening for receiving a biologicalsample and a plug assembly. The plug assembly can include a post havinga fluid vent that is configured to at least partially associate with theopening of the sample collection vessel and a plug associated with thepost that obscures the fluid vent in a closed configuration of the plugassembly. The biological sample collection system can additionallyinclude a sealing cap configured to associate with the plug assembly andwith the sample collection vessel. The sealing cap can include a reagentchamber for storing a measure of sample preservation reagent.Associating the sealing cap with the sample collection vessel can causea physical rearrangement of the plug assembly such that the plug isremoved from association with the post, thereby permitting samplepreservation reagent to pass from the regent chamber to the samplecollection vessel.

The present disclosure also includes methods for collecting andpreserving a biological sample. An exemplary method includes receiving abiological sample at a disclosed sample collection system andassociating a sealing cap with the sample collection vessel, forexample, to cause a selectively movable valve associated with thesealing cap to open and thereby release sample preservation reagent heldwithin the sealing cap into the sample collection chamber or to causethe plug of a plug assembly to dislodge, thereby releasing reagent heldwithin the sealing cap into the sample collection chamber.

Accordingly, systems, methods, and kits for collecting a biologicalsample are disclosed herein. This summary is provided to introduce aselection of concepts in a simplified form that are further describedbelow in the detailed description. This summary is not intended toidentify key features or essential features of the claimed subjectmatter, nor is it intended to be used as an indication of the scope ofthe claimed subject matter.

Additional features and advantages of the disclosure will be set forthin the description which follows, and in part will be obvious from thedescription, or may be learned by the practice of the disclosure. Thefeatures and advantages of the disclosure may be realized and obtainedby means of the instruments and combinations particularly pointed out inthe appended claims. These and other features of the present disclosurewill become more fully apparent from the following description andappended claims or may be learned by the practice of the disclosure asset forth hereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

In order to describe the manner in which the above recited and otheradvantages and features of the disclosure can be obtained, a moreparticular description of the disclosure briefly described above will berendered by reference to specific embodiments thereof, which areillustrated in the appended drawings. It is appreciated that thesedrawings depict only typical embodiments of the disclosure and are nottherefore to be considered to be limiting of its scope. The disclosurewill be described and explained with additional specificity and detailthrough the use of the accompanying drawings in which:

FIG. 1A illustrates a perspective view of an unassembledthree-dimensional model of an exemplary sample collection system withthe depicted sealing cap unsecured from the sample collection vessel inaccordance with one or more embodiments of the present disclosure.

FIG. 1B illustrates a cross-sectional view of an assembledthree-dimensional model of the sample collection system of FIG. 1A withthe depicted sealing cap secured to a sample collection vessel and theassociated valve in a closed configuration in accordance with one ormore embodiments of the present disclosure.

FIG. 2A illustrates a cross-sectional view of the selectively movablevalve of FIG. 1B depicted in a closed configuration in accordance withone or more embodiments of the present disclosure.

FIG. 2B illustrates a cross-sectional view of the selectively movablevalve of FIGS. 1B and 2A isolated away from other components of thesample collection system and depicted in a closed configuration inaccordance with one or more embodiments of the present disclosure.

FIG. 2C illustrates a cross-sectional view of the selectively movablevalve of FIGS. 1B and 2A isolated away from other components of thesample collection system and depicted in an open configuration inaccordance with one or more embodiments of the present disclosure.

FIGS. 3A and 3B illustrate perspective views of a core component of aselectively movable valve in accordance with one or more embodiments ofthe present disclosure.

FIGS. 4A and 4B illustrate perspective views of a collar component of aselectively movable valve in accordance with one or more embodiments ofthe present disclosure.

FIG. 5A illustrates a cross-sectional view of an assembledthree-dimensional model of another sample collection system with thedepicted sealing cap secured to a sample collection vessel and theassociated plug assembly in a closed configuration.

FIG. 5B is a zoomed view of a portion of the plug assembly and sealingcap as shown in FIG. 5A.

FIG. 6 illustrates a three-dimensional rendering of an exemplary plug.

FIGS. 7A and 7B illustrate perspective views of an exemplary post of aplug assembly.

DETAILED DESCRIPTION

Embodiments of the present disclosure address one or more problems inthe art of systems, kits, and/or methods for collecting and preserving abiological sample. A biological sample can be collected and its contentsevaluated for various reasons, including, for example, identifying orcharacterizing a causative agent of disease (e.g., for treatment of theaffected individual, for epidemiological reasons, etc.) or for geneticanalysis of a subject's nucleic acid (e.g., genetic phylotyping, geneexpression studies, genome sequencing, etc.). In most instances,including within the foregoing examples, it is desirous that thefidelity of the biological sample be maintained so that it retains itsprobative value. However, collecting and preparing biological samplesfor analysis has traditionally been a complex endeavor for the skilledtechnician or specialized professional. This is problematic for obviousreasons, including the time and cost associated with individuallycollecting and transporting biological samples, particularly when thesubjects reside in disparate rural locations and require service frompersonnel with the proper skill set to properly collect and preserve thebiological sample.

Embodiments of the present disclosure provide sample collection andpreservation systems and kits, and methods for using the same, whichaddress one or more of the foregoing problems. For example, utilizingsystems, kits, and methods for collecting and preserving biologicalsamples, as disclosed herein, removes the need of specialized personnelwhen collecting and initially preserving a biological sample.Furthermore, the disclosed embodiments simplify sample collection andpreservation, which decreases the likelihood that even an unskilled userwill err when collecting and preserving a biological sample.

As an illustrative example of the foregoing, biological samplecollection kits disclosed herein include at least a two-piece samplecollection and preservation system. A first portion includes a samplecollection vessel or vessel, which can be detachably associated with afunnel. When used, the funnel acts to guide the receipt of a biologicalsample from a user into the sample collection chamber of the collectionvessel or vessel. The funnel can also make it easier for a user toengage the collection vessel and deposit a biological sample into thesample collection chamber. After depositing the requisite amount ofbiological sample (which may be indicated by a mark on the samplecollection vessel), a user can remove the funnel (if used) and associatethe second portion of the two-piece sample preservation system—e.g., asealing cap associated with a selectively movable valve or plugassembly—with the collection vessel. The reagent chamber of the sealingcap is pre-filled with a predetermined amount of sample preservationreagent, and as the sealing cap is drawn down to seal the receivedbiological sample within the sample collection chamber of the collectionvessel, the selectively movable valve or plug assembly enters an openconfiguration and the preservation reagent is released from the reagentchamber, through fluid vents in the valve core or plug assembly post,and into the sample collection chamber where it mixes with and preservesthe received biological sample.

As described in more detail below, the selectively movable valves andvalve assemblies can independently be opened (depending on theembodiment incorporating the same) to release reagents from the reagentchamber into the sample collection chamber.

With respect to embodiments having a selectively movable valve, thecollar of the selectively movable valve is mechanically interlocked(e.g., via a friction fit) with the sealing cap such that the collarmoves in unison with the sealing cap. The collar can be annular andsurround the valve core forming a fluid tight connection therebetween. Aflange associated with the core is sized and shaped to fit over theopening of the sample collection vessel (or structure associatedtherewith), preventing its ingress into the sample collection chamber.Upon association of the sealing cap with the sample collection vessel,the core flange abuts the opening of the sample collection chamber. Asthe sealing cap is further secured to the sample collection vessel(e.g., by threaded engagement), the collar moves in conjunction with thesealing cap, and the core remains stationary in relation to the samplecollection vessel. In this way, the core moves (e.g., translateslongitudinally) relative to the collar and sealing cap, causing theselectively movable valve to open (e.g., by undergoing a physicalrearrangement). The independent movement of core relative to the sealingcap can be enabled by, for example, the force (e.g., frictional force orforce required to overcome a mechanical interlock) between the core andthe collar (which forms a fluid tight connection) being less than theforce between the attachment mechanisms of the sealing cap and samplecollection device. When moved to an open configuration, the previouslyobstructed fluid vents provided by the core are at least partiallyunobstructed, thereby creating a conduit for communicating the samplepreservation solution from the reagent chamber of the sealing cap intoto the sample collection chamber.

It should be appreciated that in some embodiments, opening of theselectively movable valve is reversible. That is, the selectivelymovable valve can be moved from an open configuration to a closedconfiguration. For example, embodiments of the disclosed apparatus canbe configured so that the core can be manually repositioned within thecollar (e.g., by applying a longitudinal force against the head memberof the core and toward the collar), thereby returning the selectivelymovable valve to the closed configuration.

With respect to embodiments having a plug assembly, a collar of the plugassembly is mechanically interlocked (e.g., via a friction fit) with thesealing cap such that the collar moves in unison with the sealing cap.The collar can be annular and surround the post of the plug assembly andmay form a fluid tight connection therebetween. Additionally, oralternatively, a plug can be positioned within the aperture formed bythe collar, forming a fluid tight connection therebetween. The plug canhave a head sized and shaped to overlay a portion of the top surface ofthe collar (forming a fluid tight connection therebetween) and/or canhave a plug body sized and shaped to fit within the aperture formed bythe collar such that a fluid tight connection is formed between the plugbody and a sidewall of the collar (e.g., a sidewall defining theaperture). A flange associated with the post is sized and shaped to fitover the opening of the sample collection vessel (or structureassociated therewith), preventing its ingress into the sample collectionchamber. Upon association of the sealing cap with the sample collectionvessel, the post flange abuts the opening of the sample collectionchamber. As the sealing cap is further secured to the sample collectionvessel (e.g., by threaded engagement), the collar moves in conjunctionwith the sealing cap, and the post remains stationary. In this way, thepost moves (e.g., translates longitudinally) relative to the collar andsealing cap, causing the post to abut against and apply pressure to theplug, eventually causing the plug to dislodge from the collar and enterinto the reagent chamber. The independent movement of post relative tothe sealing cap can be enabled by, for example, the force (e.g.,frictional force or force required to overcome a mechanical interlock)between the post and the collar and/or plug (which forms a fluid tightconnection) being less than the force between the attachment mechanismsof the sealing cap and sample collection device. When moved to an openconfiguration, the previously obstructed fluid vent formed by the postis at least partially unobstructed, thereby creating a conduit forcommunicating the sample preservation solution from the reagent chamberof the sealing cap into to the sample collection chamber.

As can be appreciated from the foregoing, in addition to alternativeand/or additional embodiments provided herein, the systems, kits, andmethods of the present disclosure can be used by skilled or unskilledindividuals with reduced likelihood of error associated with collectingand at least initially preserving a biological sample. Accordingly,implementations of the present disclosure can reduce the cost associatedwith procuring biological samples for diagnostic, scientific, or otherpurposes and can increase the geographic reach of potential samplecollection areas without the need of establishing the necessaryinfrastructure (e.g., controlled environments conducive to samplecollection and preservation, skilled personnel to physically collect,transport, and/or preserve the biological samples, etc.).

As used herein, the term “biological sample” can include any cell,tissue, or secretory fluid (whether host or pathogen related) that canbe used for diagnostic, prognostic, genetic, or other scientificanalysis. This can include, for example, a human cell sample such asskin. It can also include a non-human cell sample that includes any of abacterium, virus, protozoa, fungus, parasite, and/or other prokaryoticor eukaryotic symbiont, pathogen, or environmental organism. The term“biological sample” is also understood to include fluid samples such asblood, urine, saliva, and cerebrospinal fluid and extends to otherbiological samples including, for example, mucus from the nasopharyngealregion and the lower respiratory tract (i.e., sputum).

As used herein, the “probative component” of the biological samplerefers generally to any protein, nucleic acid, surface moiety, or othercompound that can be isolated from the biological sample. Preferably,the probative component is or includes nucleic acid, more preferablyDNA. In a preferred embodiment, the biological sample is or includessaliva, which presumptively contains a preferable probative component inthe form of the user's genetic material (e.g., DNA and RNA).

Sample Collection Systems and Kits Having a Selectively Movable Valve

In one embodiment, a biological sample is collected, preserved, andstored in a collection vessel as part of a multi-piece sample collectionsystem or kit. An example of a sample collection device similar to theembodiment illustrated in FIGS. 1-4 is set forth in U.S. Design App. No.29/698,615, filed Jul. 18, 2019, which is incorporated by reference. Anexample of a sample collection device similar to the embodimentillustrated in FIGS. 5-7 is set forth in U.S. Design App. No.29/698,614, filed Jul. 18, 2019, which is incorporated by reference.

As shown in FIG. 1A, a first piece of the system 100 or kit can includea sample collection vessel 102, a second piece includes a samplecollection funnel (not shown), which may be packaged separately from orremovably connected to the collection vessel, and a third piece includesa sealing cap 110 having a reagent chamber disposed within or integratedwith the sealing cap selectively and a selectively movable valvecomprised of a core and a collar. The sealing cap 110 is configured toassociate with the sample collection vessel 102, to dispense samplepreservation reagents into the sample collection vessel 102 through theselectively movable valve, and to seal the contents of the samplecollection chamber therein.

For example, FIG. 1B illustrates a cross-sectional view of an assembledthree-dimensional model of the sample collection system 100 of FIG. 1A.The system 100 includes a sample collection vessel 102 and optionally, afunnel (not shown), which can be associated with a top portion oropening 105 of the sample collection vessel 102 and thereby allow fluidcommunication with the sample collection chamber 103 of the samplecollection vessel 102. The biological sample collection system 100 canalso include a selectively movable valve 104 comprised of a core 106 anda collar 108 associated with the sealing cap 110 that has a reagentchamber 111 disposed within or integrated with the sealing cap 110. Thesealing cap 110—together with the selectively movable valve 104—can besized and shaped to associate with a top portion of the collectionvessel 102 such that the cap 110 fits over and seals an opening 105 ofthe sample collection chamber 103 and at least a portion of the valve104 (e.g., a flange 107 of the core 106) extends over the opening 105 ofthe sample collection chamber 103.

In some embodiments, the reagent within the reagent chamber 111 includesa preservation or buffering solution that protects the integrity of theprobative component of the biological sample prior to purification ortesting. Examples of preservation reagents that can be used inconjunction with the sample collection systems described herein aredisclosed in U.S. Pat. No. 10,174,362, US Pat. Pub. No. 2019/0062806,and WO 2020/102570, which are incorporated by reference. Preservationreagents are typically chemical solutions and may contain one or moresalts (e.g., NaCl, KCl, Na₂HPO₄, KH₂PO₄, or similar, and which may, insome implementations, be combined as a phosphate buffered salinesolution, as known in the art), lysing agents (e.g., detergents such asTriton X-100 or similar), chelating agents (e.g.,ethylenediaminetetraacetic acid (EDTA), ethylene glycol-bis(β-aminoethylether)-N,N,N′,N′-tetraacetic acid (EGTA), or similar), distilled water,or other reagents known in the art.

In one or more embodiments, the reagent or buffering solution stabilizesat least one probative component within the sample (e.g., nucleic acids,such as DNA and RNA, protein, etc., and combinations thereof) duringtransfer, transportation, and/or storage at a laboratory, clinic, orother destination. After the preservation solution is added, the samplecan be stored at or below room temperature for weeks or months withoutsignificant loss of the probative component. That is, the sample canstill be utilized for diagnostic, genetic, epidemiologic, or otherpurposes for which it was collected after storage for weeks or months inthe preservation solution.

With continued reference to FIG. 1, the sealing cap 110 and a salivafunnel (not shown) can each independently attach to the samplecollection vessel 102 using a connection mechanism. The connectionmechanism can include, for example, threads, snap or press fitconnections, tongue and groove members, bayonet connection, or otherinterlocking or mechanically coupling mechanisms. For example, a funnelcan be first attached to the sample collection vessel 102 viacomplementary connection mechanisms (e.g., complementary threads; notshown). After facilitating receipt of a biological sample from a user,the funnel can be removed by reversing the complementary connectionmechanism (e.g., unscrewing the funnel; not shown), and a sealing cap110 can be secured to the collection vessel 102 using a same or similarcomplementary connection mechanism. For example, as shown in FIGS. 1Aand 1B, the sealing cap 110 can include connection members 112 (e.g.,threads) located on an inner circumferential wall of the sealing cap 110that are complementary to and work in conjunction with the connectionmembers 114 (e.g., complementary threads) disposed on an exteriorsurface of the sample collection vessel 102.

In some embodiments, the connection mechanism between the funnel andcollection vessel is different than the connection mechanism between thesolution cap and the collection vessel. For example, the funnel may bepress fit or snap fit onto the collection vessel, whereas the solutioncap is rotationally secured through engagement of complementary threadslocated on an exterior portion of the collection vessel and an interiorportion of the solution cap or vice versa. Regardless of the attachmentmechanism used, a sample preservation fluid can be introduced into thesample collection chamber 103 and mixed with the deposited biologicalsample as a result of the sealing cap 110 being attached to the samplecollection vessel 102. As provided earlier, this can be due to theselectively movable valve 104 opening and allowing reagent to bereleased through fluid vent 116 defined by the open valve 104 and intothe sample collection chamber 103.

The sealing cap 110 is configured to receive a measure of reagents intothe reagent chamber 111, and as shown by the cross-sectional views ofthe assembled sample collection system 100 in FIG. 1B, a selectivelymovable valve 104 is associated with the sealing cap 110. The collar 108can be snap-fittingly received into the sealing cap 110, creating afluid tight connection therebetween. As illustrated, the collar 108includes a retaining ring or flange that engages the sealing cap 110 tostabilize the collar 108.

As further illustrated by FIGS. 2A-2C, the core 106 defines a fluid vent116, and when the valve 104 is in a closed configuration (as shown inFIGS. 2A and 2B), any reagent disposed within the reagent chamber 111 isretained and sealed within the reagent chamber 111. The valve 104 isshown in FIGS. 1B, 2A, and 2B as being aligned in a closedconfiguration. However, as shown in FIG. 2C, the selectively movablevalve 104 can be arranged in an open configuration. When associated withthe sealing cap 110 in an open configuration, reagent may be transferredfrom the reagent chamber 111 to the sample collection chamber 103through the vent(s) 116.

That is, the fluid vent(s) 116 can be obstructed by the collar 108 ofthe selectively movable valve 104 when the valve 104 is in a closedconfiguration, as illustrated in FIGS. 2A and 2B. In this state, theinteraction between the interior sidewall of the collar 108 and the headmember 109 of the core 106 creates a fluid tight connection—at least atand/or around the fluid vent 116. The fluid tight connection between thecollar 108 and the core 106 prevents the premature or unintentionalexpulsion of reagent from the reagent chamber 111.

It should be appreciated that in some embodiments, the fluid vent(s)and/or structure of the core can beneficially act as an agitator offluids entering and/or traversing between the sample collection chamberand the sealing cap.

As the complementary threads 114, 112 between the sealing cap 110 andthe sample collection vessel 102 are inter-engaged and the sealing cap110 is advanced towards the sample collection vessel 102, the proximalflange 107 of the core 106 engages the upper lip of the samplecollection tube defining the opening 105 thereof. As the sealing cap 110is further secured to and moved toward the sample collection vessel 102(e.g., by threaded engagement), the collar 108 moves in conjunction withthe sealing cap 110, and the core 106 remains stationary relative to thesample collection vessel 102. In this way, the collar 108 is displacedlongitudinally relative to the core 106, causing the selectively movablevalve assembly 104 to enter an open configuration (e.g., by undergoing aphysical rearrangement as shown in FIG. 2C). When moved to the openconfiguration, the previously obstructed fluid channels or vents 116formed within the core 106 allow fluid communication between the reagentchamber 111 and the sample collection chamber 103.

The fluid channels/vents 116 formed within the core 106, and the variousother components of the core 106 discussed above are illustrated in theperspective views of an exemplary core 106 in FIGS. 3A and 3B.Similarly, the collar 108 of FIGS. 1 and 2 is illustrated in multipleperspective views comprising FIGS. 4A and 4B.

As the core 106 transitions from the closed configuration to the openconfiguration, an annular retention element 113 disposed on the body ofthe core 106 forms a fluid tight seal with the inner sidewall of thecollar 108. Upon fully entering the open configuration, the annularretention element 113 is flush with the top surface of the collar 108and maintains a fluid-tight connection therebetween. Accordingly, thereis no pooling of sample preservation reagent (from the fluid chamber)between the interior sidewall of the collar 108 and the exteriorsidewall of the core 106. Instead, the sample preservation reagent isdirected from the reagent chamber 111, through the fluid vents 116formed within the core 106, and into the sample collection chamber 103it mixes with and preserves the received biological sample. In this way,the valve assembly 104 can move from a closed configuration to an openconfiguration when the sealing cap 110 is sealed onto the samplecollection vessel 102.

In some embodiments, the resistive force derived from the engagement ofthe collar 108 with the chamber sidewall is the result of aninterference fit formed between the collar 108 and the chamber sidewall.The interference fit can, in some embodiments, be a fluid-tight fit.

In some embodiments, the rotational distance required to open theselectively movable valve 104 is proportional to the distance requiredto at least partially unobstruct the fluid vent 116. This distance maybe the same or less than the distance traversed by the sealing cap 110from initial engagement of the connection members 114, 112 to a sealedposition of the cap 110 and vessel 102. However, it should beappreciated that although a plurality of fluid vents 116 are illustratedin the Figures, in some embodiments there can be fewer (e.g., a singlefluid channel/vent or more than four fluid channels/vents).

Sample Collection Systems and Kits Having a Plug Assembly

Referring now to FIGS. 5-7, some sample collection systems can include aplug assembly. As shown, the hollow collar 202 of the plug assembly ismechanically interlocked (e.g., via a friction fit) with the sealing cap210 such that the hollow collar 202 moves in unison with the sealing cap210 toward the sample collection vessel 201 when the sealing cap 210 isused to seal the sample collection vessel 201. As shown in FIGS. 5A, 5B,and 6, the plug 204 includes a cylindrical body and two flanges. Anupper flange 205 is sized and shaped to span the aperture formed by thehollow collar 202 and can, as shown, extend beyond the diameter of thecollar's aperture such that a bottom surface of the upper flange 205 canform a fluid tight seal with the upper surface of the hollow collar 202.A lower flange 207 of the plug 204 extends radially from the cylindricalbody and is sized and shaped to engage the sidewall of the hollow collar202 defining the aperture.

The post 206 defines a plurality of fluid vents 212 that passuninterrupted through the body of the post 206. A cylindrical upperportion of the post is sized and shaped to fit within the aperturedefined by the hollow collar 202. A leading edge 208 of the upperportion of the post 206 is configured to associate with a bottom surface(e.g., the lower flange 207) of the plug 204. In the embodiment shown inFIGS. 5A and 5B, the leading edge 208 of the upper portion includes acrown that engages an indent formed within the bottom portion of theplug 204. In some embodiments, the outer rim of the crown is sized andshaped to engage the lower flange 207 of the plug 204. The post 206additionally includes a base portion or flange 209 that is sized andshaped to engage the opening of the sample collection vessel (orstructure associated therewith).

When provided to a user for collecting a biological sample (typicallysaliva), the plug-disc device (e.g., device 200) is included in twoparts: (1) the sample collection vessel 201 and (2) the sealing cap 210,which includes the seal assembly (in a sealed configuration) forming afluid-tight seal over the reagent chamber where it retains preloadedsample preservation solution. The user can deposit the biological samplewithin the sample collection tube, and following use, the sealing cap isassociated with the sample collection tube to seal the receivedbiological sample.

Upon association of the sealing cap 210 with the sample collectionvessel 201, the base portion or flange 209 of the post 206 engages theupper lip of the sample collection vessel defining the opening thereof.As the sealing cap 210 is further secured to and moved toward the samplecollection vessel 201 (e.g., by threaded engagement), the hollow collar202 moves in conjunction with the sealing cap 210, and the post 206remains stationary relative to the sample collection vessel 201. In thisway, the hollow collar 202 is displaced longitudinally with respect tothe post 206, and this causes the leading edge 208 (e.g., crown portion)of the post 206 to press against the bottom side (e.g., lower flange207) of the plug 204. At some point, the rotational force of tighteningthe sealing cap 210 is translated into a force sufficient to cause theplug 204 to disengage from the hollow collar 202. At first, the upperflange 205 is translated away from the hollow collar 202, therebybreaking the fluid-tight seal formed therebetween, while the second,lower flange 207 remains in contact with the sidewall of the hollowcollar 202. Eventually, however, the post 206 presses—and moves—the plug204 such that the lower flange 207 becomes disengaged from the sidewall,causing the plug 204 to be ejected into the reagent chamber of thesealing cap 210.

Once the plug 204 is disengaged from the hollow collar 202, the upperend of the post 206 is brought into fluid communication with the reagentchamber—essentially converting the seal assembly to an unsealedconfiguration. In this unsealed configuration, the fluid vents 212 areunobstructed and act as channels for transporting the samplepreservation solution from the reagent chamber to the sample collectionvessel 201. The body of the post 206 forms a fluid tight seal with theinner sidewall of the hollow collar 202, forcing egress of samplepreservation solution through the fluid vents/channels 212. Accordingly,there is no pooling of sample preservation reagent (from the reagentchamber) between the interior sidewall of the hollow collar 202 and theexterior sidewall of the post 206. Instead, the sample preservationreagent is directed from the reagent chamber, through the fluid vents212 formed within the post 206, and into the sample collection vessel201 where it mixes with and preserves the received biological sample. Inthis way, the seal assembly can move from a sealed configuration to anunsealed configuration when the sealing cap 210 is sealed onto thesample collection vessel 201.

In some embodiments, the seal assembly can be reversibly sealed andunsealed. That is, the plug 204 from the seal assembly can be seriallyadded and removed from the opening of the hollow collar 202 to iteratefrom the sealed configuration to the unsealed configuration. Forexample, associating the sealing cap 210 with the sample collectionvessel 201 can cause the plug 204 to disengage, thereby causing the sealassembly to transition from the sealed configuration to the unsealedconfiguration. In the unsealed configuration, the post 206 can beretracted and the plug 204 again placed within the hollow collar 202 totransition the seal assembly from the unsealed configuration to thesealed configuration.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which the present disclosure pertains.

It will also be appreciated that systems, devices, products, kits,methods, and/or processes, according to certain embodiments of thepresent disclosure may include, incorporate, or otherwise compriseproperties, features (e.g., components, members, elements, parts, and/orportions) described in other embodiments disclosed and/or describedherein. Accordingly, the various features of certain embodiments can becompatible with, combined with, included in, and/or incorporated intoother embodiments of the present disclosure. Thus, disclosure of certainfeatures relative to a specific embodiment of the present disclosureshould not be construed as limiting application or inclusion of saidfeatures to the specific embodiment. Rather, it will be appreciated thatother embodiments can also include said features, members, elements,parts, and/or portions without necessarily departing from the scope ofthe present disclosure.

Moreover, unless a feature is described as requiring another feature incombination therewith, any feature herein may be combined with any otherfeature of a same or different embodiment disclosed herein. Furthermore,various well-known aspects of illustrative systems, methods, apparatus,and the like are not described herein in particular detail in order toavoid obscuring aspects of the example embodiments. Such aspects are,however, also contemplated herein.

The present disclosure may be embodied in other specific forms withoutdeparting from its spirit or essential characteristics. The describedembodiments are to be considered in all respects only as illustrativeand not restrictive. The scope of the invention is, therefore, indicatedby the appended claims rather than by the foregoing description. Whilecertain embodiments and details have been included herein and in theattached disclosure for purposes of illustrating embodiments of thepresent disclosure, it will be apparent to those skilled in the art thatvarious changes in the methods, products, devices, and apparatusdisclosed herein may be made without departing from the scope of thedisclosure or of the invention, which is defined in the appended claims.All changes which come within the meaning and range of equivalency ofthe claims are to be embraced within their scope.

What is claimed is:
 1. A method of collecting and preserving abiological sample, comprising: providing a sample collection vessel thatincludes a top portion, an opening at the top portion, a samplecollection chamber, and a funnel removably attached to the top portionand having a sample receiving opening; providing a sealing cap thatincludes a reagent chamber, a valve, and a sample preservation reagentin the reagent chamber; placing the biological sample through the samplereceiving opening of the funnel, the funnel guiding the biologicalsample through the opening at the top portion of the sample collectionvessel and into the sample collection chamber; removing the funnel fromthe sample collection vessel, thereby exposing the opening at the topportion of the sample collection vessel; and associating the sealing capwith the sample collection vessel so that the sealing cap fits over andseals the opening at the top portion of the sample collection vessel toseal the contents of the sample collection chamber, wherein associatingthe sealing cap with the sample collection vessel opens the valve andpermits the sample preservation reagent to pass from the reagent chamberinto the sample collection chamber to mix with and preserve thebiological sample.
 2. The method of claim 1, wherein the valve of thesealing cap is a valve assembly configured to retain the samplepreservation reagent within the reagent chamber when the valve assemblyis in a closed configuration and release the sample preservation reagentfrom the reagent chamber into the sample collection chamber when thevalve assembly is in an open configuration.
 3. The method of claim 2,the valve assembly comprising: a core configured to associate with theopening at the top portion of the sample collection vessel; one or morefluid vents through the core; and a collar disposed about the core andwhich forms a fluid tight seal with the core and obstructs the one ormore fluid vents to retain the sample preservation reagent within thereagent chamber when the valve assembly is in the closed configuration.4. The method of claim 3, wherein associating the sealing cap with thesample collection vessel causes a physical rearrangement of the corerelative to the collar to put the valve assembly in the openconfiguration in which the one or more fluid vents are at leastpartially unobstructed and moved into fluid communication with thereagent chamber.
 5. The method of claim 4, wherein the physicalrearrangement includes translational movement of the core along alongitudinal axis relative to the sealing cap and in a directionopposite the direction of the sealing cap.
 6. The method of claim 3,wherein the core and the collar of the valve assembly are configured sothat when the sealing cap is associated with the top portion of thesample collection vessel a flange of the core engages the top portion ofthe sample collection vessel to prevent the core from traversing theopening at the top portion of the sample collection vessel as thesealing cap is moved longitudinally toward the sample collection vessel.7. The method of claim 3, wherein the core comprises a head memberconfigured to form a fluid-tight seal with the collar when the valveassembly is in the closed configuration, and wherein one or more of thecollar or the head member comprises an annular retention elementconfigured to maintain a fluid-tight seal between the collar and thehead member when the valve assembly is in the closed configuration. 8.The method of claim 3, wherein the plurality of fluid vents are disposedradially about the core with each comprising an entrance aperturethrough a side of the core and an exit aperture through a distal end ofthe core.
 9. The method of claim 8, wherein the fluid vents span aninterior portion of the core and are uninterrupted between the entranceaperture and the exit aperture of each fluid vent.
 10. The method ofclaim 1, wherein the funnel is removably attached to the samplecollection vessel by a connection mechanism selected from the groupconsisting of threads, snap fit connections, press fit connections,tongue and groove members, bayonet connections, and interlocking ormechanically coupling mechanisms.
 11. The method of claim 1, wherein thefunnel has a complementary connection mechanism at a distal end forremoveable attachment to the top portion of the sample collectionvessel, a receiving opening at a proximal end for receiving thebiological sample from the user, and an exit opening at the distal endthrough which the biological sample exits when being guided through theopening of sample collection vessel and into the sample collectionchamber.
 12. The method of claim 1, wherein the sample collection vesselincludes a connection member on an exterior surface of the top portionof the sample collection vessel adjacent to the opening, and wherein thesealing cap comprises a complementary connection member located on aninner wall of the sealing cap that is configured to associate with theconnection member of the sample collection vessel in order to couple thesealing cap to the sample collection vessel.
 13. The method of claim 12,wherein the connection member of the sample collection vessel comprisesa ridge projecting away from the sample collection vessel or adepression within the sample collection vessel and the complementaryconnection member of the sealing cap comprises a hook or ridge sized andshaped to engage the connection member of the sample collection vessel.14. The method of claim 12, wherein the connection member and thecomplementary connection member each comprise complementary threads,wherein the complementary threads of the connection member compriseexternal threads of the sample collection vessel, and wherein thecomplementary threads of the complementary connection member compriseinternal threads of the sealing cap.
 15. The method of claim 1, whereinthe sample collection vessel includes a generally cylindrical portionhaving a generally circular cross section of constant diameter extendingfrom the top portion of the sample collection vessel, exclusive of anyconnection member or mechanism, to a portion of the sample collectionvessel defining the sample collection chamber.
 16. A method ofcollecting and preserving a biological sample, comprising: providing asample collection kit, which is comprised of: vessel that includes a topportion, an opening at the top portion, and a sample collection chamber;a funnel having a sample receiving opening and being configured toremovably attach to the top portion of the sample collection chamber andprovide fluid communication with the sample collection chamber; and asealing cap that includes a reagent chamber, a valve, and a samplepreservation reagent in the reagent chamber; removably attaching thefunnel to the top portion of the sample collection vessel to providefluid communication between the funnel and the sample collectionchamber; placing the biological sample through the sample receivingopening of the funnel, the funnel guiding the biological sample throughthe opening at the top portion of the sample collection vessel and intothe sample collection chamber; removing the funnel from the samplecollection vessel, thereby exposing the opening at the top portion ofthe sample collection vessel; and associating the sealing cap with thesample collection vessel so that the sealing cap fits over and seals theopening at the top portion of the sample collection vessel to seal thecontents of the sample collection chamber, wherein associating thesealing cap with the sample collection vessel opens the valve andpermits the sample preservation reagent to pass from the reagent chamberinto the sample collection chamber to mix with and preserve thebiological sample.
 17. The method of claim 16, wherein the valve of thesealing cap is a valve assembly configured to retain the samplepreservation reagent within the reagent chamber when the valve assemblyis in a closed configuration and release the sample preservation reagentfrom the reagent chamber into the sample collection chamber when thevalve assembly is in an open configuration.
 18. The method of claim 17,the valve assembly comprising: a core configured to associate with theopening at the top portion of the sample collection vessel; one or morefluid vents through the core; and a collar disposed about the core andwhich forms a fluid tight seal with the core and obstructs the one ormore fluid vents to retain the sample preservation reagent within thereagent chamber when the valve assembly is in the closed configuration,wherein associating the sealing cap with the sample collection vesselcauses a physical rearrangement of the core relative to the collar toput the valve assembly in the open configuration in which the one ormore fluid vents are at least partially unobstructed and moved intofluid communication with the reagent chamber.
 19. The method of claim18, wherein the funnel is removably attachable to the sample collectionvessel by a connection mechanism selected from the group consisting ofthreads, snap fit connections, press fit connections, tongue and groovemembers, bayonet connections, and interlocking or mechanically couplingmechanisms.
 20. The method of claim 16, wherein the funnel has acomplementary connection mechanism at a distal end for removeableattachment to the top portion of the sample collection vessel, areceiving opening at a proximal end for receiving the biological samplefrom the user, and an exit opening at the distal end through which thebiological sample exits when being guided through the opening of samplecollection vessel and into the sample collection chamber.
 21. The methodof claim 16, wherein the sample collection vessel includes a connectionmember on an exterior surface of the top portion of the samplecollection vessel adjacent to the opening, and wherein the sealing capcomprises a complementary connection member located on an inner wall ofthe sealing cap and that is configured to associate with the connectionmember of the sample collection vessel in order to couple the sealingcap to the sample collection vessel.